Project Summary An estimated 200,000 anterior cruciate ligament (ACL) injuries occur in the United States each year. ACL injury results in instability, pain, damage to the meniscus, and early-onset osteoarthritis (OA). Although reconstruction is commonly performed after ACL injury, the long-term development of OA after surgery remains a major concern. This is a significant problem because of the young age of most patients undergoing ACL reconstruction (between 15 and 25 years old). Because early-onset OA is devastating to such a young population, there is an urgent need to reduce the incidence of non-contact ACL injuries, which comprise 70% of all ACL injuries. Although some prevention programs have demonstrated encouraging results, others have been less successful, and high rates of non- contact ACL injuries persist. This is likely due to conflicting data regarding the mechanisms of non-contact ACL injuries. A detailed understanding of what motions elevate ACL injury risk is needed to improve prevention strategies. Specifically, there is a lack of in vivo ACL strain data during dynamic, high risk activities. Thus, the objective of this study is to identify what motions elevate in vivo ACL strains during dynamic activities that are high risk for ACL injury. An innovative methodology combining marker-based motion capture, MR imaging, and static biplanar radiography will be used to measure six degrees-of-freedom knee kinematics and ACL strains throughout the entire motion cycle of dynamic jumping and cutting tasks. In addition, these measurements will be confirmed using high-speed biplanar radiography, a technique capable of capturing a portion of the motion cycle near ground impact. Our aims will address three important risk factors for ACL injury. Females are up to eight times more likely to sustain an ACL injury than males. Additionally, those who have sustained a unilateral ACL injury are at elevated risk for injury to the uninjured knee (up to 15 time compared to controls). Lastly, recent studies also suggest that fatigue is a significant factor elevating injury risk. Therefore, ACL strains and knee kinematics will be compared between females and males (Aim 1), the uninjured knees of subjects with and without prior ACL injuries (Aim 2), and subjects before and after completing a fatigue protocol (Aim 3). Our overall hypothesis is that landing with less knee flexion and more valgus increases ACL strains and elevates ACL injury risk. Understanding what motions elevate in vivo ACL strains during dynamic activities is a critical first step in preventing ACL injuries. In particular, these measurements of in vivo ACL strains could be used to focus neuromuscular training programs on avoiding motions that predispose the ACL to injury. Furthermore, these data and this approach could be used clinically to identify individuals who are at high risk for injury and could be targeted for intervention. Thus, these data are essential to improving the efficacy of prevention programs. Reducing ACL injury rates is significant due to the devastating early-onset OA observed in these patients.